Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor peripheral blood progenitor cell mobilization

James L. Gajewski, Gabriela Rondon, Michele L. Donato, Paolo Anderlini, Martin Korbling, Cindy Ippoliti, Mark Benyunes, Langdon L. Miller, Denise LaTemple, Denny Jones, Mark Ashby, Sue Hellmann, April Durett, Jo Lauppe, Deborah Geisler, Issa F. Khouri, Sergio A. Giralt, Borje Andersson, Naoto T. Ueno, Richard Champlin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 μg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 μg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached ≥2 × 109/L; leukapheresis was continued until acquisition of a target dose of ≥5 × 106 CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 × 106 CD34+ cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 × 106 cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after highdose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 × 109/L and a platelet count of 20 × 109/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.

Original languageEnglish (US)
Pages (from-to)550-556
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume8
Issue number10
StatePublished - 2002
Externally publishedYes

Fingerprint

Thrombopoietin
Granulocyte Colony-Stimulating Factor
Leukapheresis
Combination Drug Therapy
Blood Cells
Stem Cells
Drug Therapy
Cyclophosphamide
Neutrophils
Thiotepa
Transplants
Carmustine
Etoposide
Platelet Count
Leukocyte Count
Cisplatin
Anti-Idiotypic Antibodies
Blood Platelets
Breast Neoplasms
Safety

Keywords

  • Autologous hematopoietic progenitor cell transplants
  • Breast cancer
  • Leukapheresis
  • Recombinant human thromnbopoietin
  • Thrombopoiesis

ASJC Scopus subject areas

  • Transplantation

Cite this

Gajewski, J. L., Rondon, G., Donato, M. L., Anderlini, P., Korbling, M., Ippoliti, C., ... Champlin, R. (2002). Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor peripheral blood progenitor cell mobilization. Biology of Blood and Marrow Transplantation, 8(10), 550-556.

Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor peripheral blood progenitor cell mobilization. / Gajewski, James L.; Rondon, Gabriela; Donato, Michele L.; Anderlini, Paolo; Korbling, Martin; Ippoliti, Cindy; Benyunes, Mark; Miller, Langdon L.; LaTemple, Denise; Jones, Denny; Ashby, Mark; Hellmann, Sue; Durett, April; Lauppe, Jo; Geisler, Deborah; Khouri, Issa F.; Giralt, Sergio A.; Andersson, Borje; Ueno, Naoto T.; Champlin, Richard.

In: Biology of Blood and Marrow Transplantation, Vol. 8, No. 10, 2002, p. 550-556.

Research output: Contribution to journalArticle

Gajewski, JL, Rondon, G, Donato, ML, Anderlini, P, Korbling, M, Ippoliti, C, Benyunes, M, Miller, LL, LaTemple, D, Jones, D, Ashby, M, Hellmann, S, Durett, A, Lauppe, J, Geisler, D, Khouri, IF, Giralt, SA, Andersson, B, Ueno, NT & Champlin, R 2002, 'Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor peripheral blood progenitor cell mobilization', Biology of Blood and Marrow Transplantation, vol. 8, no. 10, pp. 550-556.
Gajewski, James L. ; Rondon, Gabriela ; Donato, Michele L. ; Anderlini, Paolo ; Korbling, Martin ; Ippoliti, Cindy ; Benyunes, Mark ; Miller, Langdon L. ; LaTemple, Denise ; Jones, Denny ; Ashby, Mark ; Hellmann, Sue ; Durett, April ; Lauppe, Jo ; Geisler, Deborah ; Khouri, Issa F. ; Giralt, Sergio A. ; Andersson, Borje ; Ueno, Naoto T. ; Champlin, Richard. / Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor peripheral blood progenitor cell mobilization. In: Biology of Blood and Marrow Transplantation. 2002 ; Vol. 8, No. 10. pp. 550-556.
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abstract = "This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 μg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 μg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached ≥2 × 109/L; leukapheresis was continued until acquisition of a target dose of ≥5 × 106 CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91{\%} required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69{\%} of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 × 106 CD34+ cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 × 106 cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after highdose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 × 109/L and a platelet count of 20 × 109/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.",
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AU - Gajewski, James L.

AU - Rondon, Gabriela

AU - Donato, Michele L.

AU - Anderlini, Paolo

AU - Korbling, Martin

AU - Ippoliti, Cindy

AU - Benyunes, Mark

AU - Miller, Langdon L.

AU - LaTemple, Denise

AU - Jones, Denny

AU - Ashby, Mark

AU - Hellmann, Sue

AU - Durett, April

AU - Lauppe, Jo

AU - Geisler, Deborah

AU - Khouri, Issa F.

AU - Giralt, Sergio A.

AU - Andersson, Borje

AU - Ueno, Naoto T.

AU - Champlin, Richard

PY - 2002

Y1 - 2002

N2 - This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 μg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 μg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached ≥2 × 109/L; leukapheresis was continued until acquisition of a target dose of ≥5 × 106 CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 × 106 CD34+ cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 × 106 cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after highdose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 × 109/L and a platelet count of 20 × 109/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.

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KW - Autologous hematopoietic progenitor cell transplants

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KW - Recombinant human thromnbopoietin

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